PLX266884

GSE90533: An HDAC3-PROX1 Corepressor Module Acts on HNF4 to Control Hepatic Triglycerides

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism we developed a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR/HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by Hepatocyte Nuclear Factor 4 (HNF4). The HDAC3-PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism. SOURCE: Manashree Damle (mdamle@mail.med.upenn.edu) - Mitch Lazar University of Pennsylvania